Enasidenib for Patients With Clonal Cytopenia of Undetermined Significance and Mutations in IDH2A Decentralized Trial

Inclusion Criteria:

• Unexplained cytopenia for at least 6 months. Cytopenia is defined as the presence of ≥1 blood count indexes below the following thresholds:

• Hgb <10 g/dL

• ANC <1.8 × 109/L

• Platelets <100 × 109/L

• IDH2 gene mutation (R140 or R172), performed locally, at a frequency ≥ 2%.

• At least 18 years of age.

• ECOG performance status 0-2

• Adequate organ function as defined below:

• AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN

• Serum total bilirubin < 1.5 x IULN (un upper limit of bilirubin 5 mg/dL isacceptable if it can be attributed to Gilbert's syndrome or erythropoiesis)

• Creatinine clearance > 50 mL/min by Cockcroft-Gault glomerular filtration rateestimation or serum creatinine ≤ 2 x IULN

• The effects of enasidenib on the developing human fetus are unknown. For thisreason, women of childbearing potential and men must agree to use adequatecontraception prior to study entry, for the duration of study participation, and for 24 months after the last dose of enasidenib. Should a woman become pregnant orsuspect she is pregnant while participating in this study, she must inform hertreating physician immediately. Men treated or enrolled on this protocol must alsoagree to use adequate contraception prior to the study, for the duration of thestudy, and for 4 months after the last dose of enasidenib.

• Ability to understand and willingness to sign an IRB approved written informedconsent document. Legally authorized representatives may sign and give informedconsent on behalf of study participants.

Exclusion Criteria:

• Indication of hematologic disease by bone marrow biopsy within 6 months of studyentry.

• Evidence of disease progression from time of bone marrow biopsy to enrollmentbased on investigator review of symptoms and complete blood counts

• Active malignancy (defined as > 1 cm disease on most recent CT scan in the past 6months).

• Currently receiving therapy for solid tumor malignancy or received within the last 6months.

• Currently receiving any other investigational agents.

• Known dysphagia, short-gut syndrome, gastroparesis, or other conditions that limitthe ingestion or gastrointestinal absorption of drugs administered orally.

• A history of allergic reactions attributed to compounds of similar chemical orbiologic composition to enasidenib or other agents used in the study.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, orcardiac arrhythmia.

• Pregnant and/or breastfeeding. Women of childbearing potential must have a negativepregnancy test within 72 hours of study entry.

• Positive direct Coombs test.